Implantable glucose monitor

ABSTRACT

Implantable device for measuring the glucose concentration of a body fluid when implanted, the device comprising a glucose measurement unit, the glucose measurement unit comprising a light source configured to emit light towards a light transmissive part of a housing of the device, the device further comprising an optical sensor configured to detect light returned through the transmissive part from the light source, and output an electrical signal based on the detected light, and a wireless communication module configured to wirelessly communicate with an external wireless communication device, wherein the wireless communication module is configured to wirelessly transmit a signal based on the electrical signal to the external wireless communication device.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 16/765,231, filed on May 19, 2020, which is the national stageentry of International Patent Application No. PCT/EP2018/081303, filedon Nov. 15, 2018, and claims priority to Application No. EP 17306606.9,filed on Nov. 21, 2017, the disclosures of which are incorporated hereinby reference.

TECHNICAL FIELD

The present disclosure relates to an implantable device for measuringthe glucose concentration of a body fluid when implanted, a systemcomprising an implantable device, and a method for measuring glucoseconcentration.

BACKGROUND

Insulin therapy often generally requires repeated blood glucosemeasurements to be taken from a diabetic patient. Diabetics with Type Idiabetes may measure blood glucose 5-9 times a day, while those withgestational diabetes may take measurements up to 11 times per day.

Known blood glucose testing methods involve collecting a blood samplefrom a patient using a lancet. Blood collection using a lancet may bepainful and unpleasant for a diabetic, particularly if a high testingfrequency is required. Repeated blood collection from a skin site maylead to the formation of scars or calluses, or increased nerve density,which in turn can make it difficult to collect blood.

SUMMARY

According to an aspect of the present disclosure, there is provided animplantable device for measuring the glucose concentration of a bodyfluid when implanted, the implantable device comprising: a glucosemeasurement unit comprising a first light source configured to emitlight towards a light transmissive part of a housing of the device and afirst optical sensor configured to detect light returned through thelight transmissive part from the first light source, and output a firstelectrical signal based on the detected light; and a wirelesscommunication module configured to wirelessly communicate with anexternal wireless communication device, wherein the wirelesscommunication module is configured to wirelessly transmit a signal basedon the first electrical signal to the external wireless communicationdevice. The implantable device allows for continuous remote monitoringof glucose levels within a patient into which the device is implanted,without the need for collecting blood samples using a lancet or similardevice.

The wireless communication module may be configured to wirelesslyreceive power from the external wireless communication device. This isadvantageous in that it provides an implantable device that does notrequire replacement of an internal power source such as anon-rechargeable battery. The implantable device may therefore berepeatedly used to monitor glucose levels over a long period of timewithout the need to replace the device due to a run-down battery. Insome examples, the device may comprise a rechargeable power source suchas a battery, wherein the power source is recharged by the powerreceived by the wireless communication module.

The implantable device may be dimensioned to be implantable into a humanblood vessel, or tissue well perfused by a body fluid such as blood.This is advantageous since it allows for an accurate measurement of thepatient's blood glucose.

An outer surface of the housing may comprise a recess, wherein therecess comprises at least part of the light transmissive part. This isadvantageous in that may facilitate movement of body fluid such as bloodor interstitial fluid around the implantable device, ensuring that thebody fluid around the device is not stagnant, and hence providing a moreaccurate glucose reading. In some examples, the outer surface of thehousing may comprise one or more projections, again to facilitatemovement of body fluid around the implantable device. In some examples,the recess may be formed from one or more protrusions of the housing.Although the presence of a recess may be described in combination withother features in various embodiments herein, the presence of the recessis not mandatory,

The implantable device may further comprise at least one lens arrangedto focus the light emitted from the first light source towards a pointoutside the housing. This allows for accurate measurement of glucoseconcentration within the body fluid surrounding the housing, whilereducing interference from external light sources such as ambient light.

The light emitted from the first light source may be linearly polarisedand emitted through the light transmissive part to a first regionoutside the housing. The first optical sensor may be configured todetect linearly polarised light returned through the transmissive partfrom the first region outside the housing that has been opticallyrotated. The first optical sensor may be further configured to outputthe first electrical signal based on the detected optically rotatedlight. This provides a simple arrangement for determining the glucoseconcentration in a body fluid.

According to some embodiments, the implantable device may furthercomprise a first linear polarizer arranged to linearly polarize thelight emitted from the first light source in a first plane, a secondlinear polarizer arranged to linearly polarize light from the firstregion outside the housing in a second plane substantially orthogonal tothe first plane, and a third linear polarizer arranged to linearlypolarize light from the first region outside the housing in a thirdplane, wherein the third plane is parallel to the first plane. Theglucose measurement unit may further comprise a second optical sensorconfigured to detect light returned through the light transmissive part,and output a second electrical signal based on the detected light. Thesecond linear polarizer may be arranged such that a first part of thelinearly polarized light emitted from the first light source to thefirst region outside the housing is incident on the second linearpolarizer. The third linear polarizer may be arranged such that a secondpart of the linearly polarized light emitted from the first light sourceto the first region outside the housing is incident on the third linearpolarizer. The first optical sensor may be arranged to detect the firstpart of the linearly polarized light passing from the first regionoutside the housing through the second linear polarizer, and the secondoptical sensor may be arranged to detect the second part of the linearlypolarized light passing from the first region outside the housingthrough the third linear polarizer. This arrangement provides a simplemeans for determining the glucose concentration in a body fluid, withimproved interference suppression.

According to some embodiments, the glucose measurement unit may furthercomprises a second light source configured to emit light through thelight transmissive part to a second region outside the housing, and asecond optical sensor configured to detect light returned through thetransmissive part, and output a second electrical signal based on thedetected light. The implantable device may further comprise a firstlinear polarizer arranged to linearly polarize light emitted from thefirst light source in a first plane, a second linear polarizer arrangedto linearly polarize light from the first region outside the housing ina second plane substantially orthogonal to the first plane, a thirdlinear polarizer arranged to linearly polarize light emitted from thesecond light source in a third plane, and a fourth linear polarizerarranged to linearly polarize light from the second region outside thehousing in a fourth plane, wherein the fourth plane is parallel to thethird plane. The second linear polarizer may be arranged such that atleast part of the linearly polarized light emitted from the first lightsource to the first region outside the housing is incident on the secondlinear polarizer. The fourth linear polarizer may be arranged such thatat least part of the linearly polarized light emitted from the secondlight source to the second region outside the housing is incident on thefourth linear polarizer. The first optical sensor may be configured tobe able to detect the at least part of the linearly polarized lightemitted from the first light source, via the second linear polarizer.The second optical sensor may be configured to be able to detect the atleast part of the linearly polarized light emitted from the second lightsource, via the fourth linear polarizer. This arrangement provides asimple arrangement for determining the glucose concentration in a bodyfluid, with improved interference suppression.

According to some embodiments, the glucose measurement unit is arefractometer. This arrangement provides a simple means for determiningthe glucose concentration in a body fluid.

The refractometer may comprise a prism, wherein the first light sourceand the prism are arranged such that the light emitted from the firstlight source is incident on a surface of the prism, via the prism, andwherein the first optical sensor is arranged to detect a portion of thelight emitted from the first light source that is reflected at thesurface of the prism, via the prism. This arrangement provides aparticularly simple arrangement for determining the glucoseconcentration in a body fluid.

According to some embodiments, the glucose measurement unit is aninfra-red spectrometer, the light emitted by the first light source isinfra-red light and is emitted through the light transmission part to aregion outside the housing, and the first optical sensor is configuredto detect infra-red light returned through the light transmissive partfrom the first light source, via the region outside the housing, andoutput a first electrical signal based on the detected light infra-redlight. This arrangement provides a simple means for determining theglucose concentration in a body fluid, with improved interferencesuppression.

According to some embodiments, the implantable device further comprisesa temperature sensor, wherein the wireless communication module isconfigured to wirelessly transmit a signal based on a temperaturemeasured by the temperature sensor to the external wirelesscommunication device. This arrangement allows for temperature effects tobe easily taken into account when processing the output of the glucosemonitoring unit to determine a glucose concentration, thus providing amore accurate value of glucose concentration.

According to some embodiments, there is provided an implantable devicefor measuring the glucose concentration of a body fluid, the devicecomprising a housing containing: a glucose measurement unit comprising:a light source configured to emit light at least to an interface betweenthe implantable device and the body fluid, when the implantable deviceis surrounded by body fluid; and an optical sensor configured to detectat least part of the light emitted from the light source via theinterface, when the implantable device is surrounded by body fluid, andoutput an electrical signal based on the detected light; and a wirelesscommunication module configured to wirelessly communicate with anexternal wireless communication device;

-   -   wherein the wireless communication module is configured to        wirelessly transmit a signal based on the electrical signal to        the external wireless communication device.

According to another aspect of the present disclosure, there is provideda system comprising an aforementioned implantable device and an externalwireless communication device, wherein the wireless communication moduleof the implantable device is configured to wirelessly transmit thesignal based on the first electrical signal to the external wirelesscommunication device. The system allows for simple and unobtrusivemeasurements of glucose concentration in a body fluid.

The external wireless communication device may be a smartphone. This isa particularly simple means for wirelessly communicating with theimplantable device.

According to another aspect of the present disclosure, there is provideda method comprising emitting light, by a first light source of animplantable device for measuring the glucose concentration of a bodyfluid when implanted, towards a light transmissive part of a housing ofthe implantable device; detecting, by a first optical sensor of theimplantable device, light returned through the transmissive part fromthe first light source; outputting, by the first optical sensor, a firstelectrical signal based on the detected light; and wirelesslytransmitting, by a wireless communication module of the implantabledevice, a signal based on the first electrical signal to an externalwireless communication device. This method allows for simple andunobtrusive measurements of glucose concentration in a body fluid.

These as well as other advantages of various aspects of the presentdisclosure will become apparent from the embodiments describedhereinafter.

BRIEF DESCRIPTION OF THE FIGURES

Exemplary embodiments of the present disclosure are described withreference to the accompanying drawings, in which:

FIG. 1A is a front view of an implantable device according toembodiments of the present disclosure;

FIG. 1B is a front view of an implantable device having a recessaccording to embodiments of the present disclosure;

FIG. 1C is a schematic side-view cross-section of the implantable deviceof FIG. 1B;

FIG. 2 is a schematic cross-section of an implantable device accordingto embodiments of the present disclosure;

FIG. 3 is a schematic cross-section of part of an implantable deviceaccording to embodiments of the present disclosure; FIG. 4 is aschematic cross-section of part of an implantable device according toembodiments of the present disclosure;

FIG. 5 is a schematic cross-section of part of an implantable deviceaccording to embodiments of the present disclosure;

FIG. 6 is a schematic cross-section of part of an implantable devicecomprising a reflectometer according to embodiments of the presentdisclosure;

FIG. 7 is a schematic cross-section of part of an implantable devicecomprising an infra-red spectrometer according to embodiments of thepresent disclosure;

FIG. 8 is a schematic cross-section of a system comprising animplantable device and an external wireless communication deviceaccording to embodiments of the present disclosure, wherein theimplantable device has been implanted into a blood vessel;

FIG. 9 is a flowchart illustrating a method for determining glucoseconcentration in a body fluid according to aspects of the presentdisclosure.

Reference will now be made in detail to the embodiments of the presentdisclosure, examples of which are illustrated in the accompanyingdrawings, wherein like reference numerals refer to like elementsthroughout.

DETAILED DESCRIPTION

An implantable device for measuring the glucose concentration of a bodyfluid when implanted is provided. A system comprising the implantabledevice and an external wireless communication device, and a method ofmeasuring the glucose concentration of a body fluid using theimplantable device and external wireless communication device are alsoprovided.

The aforementioned body fluid is a fluid within a human or animal thatcontains glucose, wherein the glucose concentration can be measured forinsulin therapy. The body fluid is preferably blood, but mayalternatively or additionally be interstitial fluid. It is preferable tomeasure the glucose concentration in the blood of a human or animalrather than the interstitial fluid because blood is generally moreresponsive to changes in glucose concentration than interstitial fluid.

FIG. 1 shows an implantable device 1 in accordance with some aspects ofthe present disclosure. The implantable device 1 has a housing 10,wherein other components of the implantable device 1 are located insidethe housing 10.

The housing 10 has a light transmissive part 12 which allows light ofone or more wavelengths to pass through from one side of the lighttransmissive part 12 to another side. Light is therefore able to passfrom outside the housing 10 to the inside of the housing 10 via thelight transmissive part 12, and vice versa. A discrete region or windowof the housing 10 may comprise the light transmissive part 12, as shownin FIG. 1A. Alternatively, the entire housing 10 may be lighttransmissive. In some examples, the light transmissive part 12 comprisesa plurality of discrete regions of the housing 10, the discrete regionsbeing separated by optically opaque parts of the housing 10.

The housing 10 is preferably made of a biocompatible material such asglass so that the implantable device 1 may be safely implanted into ahuman or animal. The use of glass for the housing 10 is advantageous inthat glass is light transmissive, and hence the housing 10 and lighttransmissive part 12 may be formed from the same material, in a singleprocess.

The implantable device 1 is to be subcutaneously implanted within ahuman or animal body. Preferably the implantable device 1 can beimplanted within a blood vessel of the human or animal, allowing formeasurement of the glucose concentration in the blood of said human oranimal. In this case, the particular body fluid being measured will beblood.

In some embodiments the implantable device 1 is dimensioned to beimplantable into a human blood vessel, such as an artery or vein. Forexample, the device may have a maximum width w along one axis of aroundless than 5 mm, preferably around less than 3 mm, and more preferablyaround 1.35 mm to 2 mm.

In some examples, the implantable device 1 configured is to be implantedinto tissue well perfused by a body fluid, such as blood. For example,the implantable device 1 may be implanted within the interstitial fluidof a human or animal, for example just under the skin. In this case, theparticular body fluid being measured is the interstitial fluid.

Once the implantable device 1 has been implanted, body fluid will comeinto contact with the light transmissive part 12 of the housing 10. Whenthe implantable device 1 has been implanted in a blood vessel, bloodwill contact the light transmissive part 12. When the implantable device1 has been implanted in interstitial fluid, interstitial fluid will becontacting the light transmissive part 12.

FIG. 1B shows an implantable device 1 similar to the implantable device1 of FIG. 1A, however an outer surface 11 of the housing 10 comprises arecess 14. FIG. 1C shows a side-view of the implantable device of FIG.1B, showing a side-view of the recess 14.

As shown in FIG. 1C, the recess 14 may comprise a first side wall 15, asecond side wall 16, and a bottom surface 17.

The recess 14 may be a groove in the outer surface 11 of the housing 10.In other embodiments, the recess 14 may be a conduit through which bodyfluid may flow from one side of the implantable device 1 to another sideof the implantable device 1. For example, the conduit may extend fromone side of the housing 10 to an opposing side of the housing 10. Therecess 14 is filled with body fluid when the implantable device 1 isimplanted.

Providing a recess 14 in the housing 10 can facilitate the movement ofbody fluid around the implantable device 1 when the device is implanted.This may be particularly advantageous if the implantable device 1 isimplanted into a blood vessel, since the recess may allow blood to flowmore easily around or through the implantable device 1. As such, bloodflow through the blood vessel is less obstructed by the implanted device1.

In some examples, the housing 10 may comprise one or more protrusions(not shown) arranged on the outer surface 11. The one or moreprotrusions may be configured to hold the implantable device 1 in afixed location within a human or animal body once implanted into saidbody. If the implantable device 1 is implanted into a blood vessel, theone or more protrusions may be configured to hold the implantable device1 in a fixed location within the blood vessel by exerting pressure onthe inner walls of the blood vessel.

The light transmissive part 12 shown in FIGS. 1B and 1C is comprised ina discrete region of the housing 10, in this case entirely within recess14. However, the light transmissive part 12 is not limited to thisarrangement and may be located in another part of the housing 10, or maycomprise the entirety of housing 10.

FIG. 2 is a schematic cross-section of an implantable device 1 accordingto embodiments of the present disclosure.

The implantable device 1 comprises a wireless communication module 20, aglucose measurement unit 30, and a housing 10 having light transmissivepart 12.

The wireless communication module 20 is configured to wirelesslycommunicate with an external wireless communication device 2 (as shownin FIG. 8 ), preferably using near field communication (NFC), but otherforms of wireless communication may be used.

The wireless communication module 20 is preferably configured towirelessly receive power from the external wireless communication 2device by electromagnetic induction.

The wireless communication module 20 comprises an antenna 22, an energystorage unit 24 such as a capacitor or rechargeable battery, and acontrol unit 26 such as an integrated circuit. The antenna 22 isconfigured to transmit and receive wireless signals, whereintransmission of wireless signals by the antenna is controlled by thecontrol unit 26. The energy storage unit 24 stores electrical energyreceived from the external wireless communication device 2 via theantenna 22. The control unit 26 may comprise a memory unit (not shown)for storing instructions to be carried out by the control unit 26,and/or data related to measurements made by the glucose measurement unit30. The control unit 26 may control one or more operations of theglucose measurement unit 30 described herein, and may carry out any ofthe method steps described herein with respect to the implantable device1.

The glucose measurement unit 30 comprises a light source 32 and anoptical sensor 34. The light source 32 may comprise one or more lightemitting diodes (LEDs), and is configured to emit light towards thelight transmissive part 12 of the housing 10, that is, from the insideof the housing 10 towards the outside of the housing 10. The lightsource 32 is preferably powered by the energy storage unit 24 andcontrolled by the control unit 26.

The optical sensor 34, also known as a light sensor, detects light byconverting received light into an electrical signal. The optical sensor34 thus outputs an electrical signal based on the detected light. Theoptical sensor 34 may comprise one or more photodetectors such asphotodiodes. The optical sensor 34 may detect light having a specificwavelength, or a range of wavelengths. The optical sensor 34 may bevariable. That is, the specific wavelength or range of wavelengthsdetected by the optical sensor 34 may be variable. The wavelength(s)detected by such an optical sensor 34 may be selected by changing avoltage applied to the optical sensor 34.

The optical sensor 34 is configured to detect light returned through thelight transmissive part 12 of the housing 10, and output an electricalsignal based on the detected light. In other words, the optical sensor34 is configured to detect light that has been emitted by the lightsource 32 from inside the housing 10 into the light transmissive part 12of the housing 10 and that has returned to the inside of the housing 10via the light transmissive part 12.

The returned light may have travelled from the light source 32 throughthe light transmissive part 12 to a region outside the housing 10,before returning back through the light transmissive part 12 to theinside of the housing 10 where it is detected by the optical sensor 34.In other examples the returned light has travelled from the light source32 through the light transmissive part 12, before being internallyreflected at a surface of the light transmissive part 12 and returningback through the light transmissive part 12 to the inside of the housing10, where it is detected by the optical sensor 34. The surface of thelight transmissive part 12 at which the light is internally reflectedforms part of the outer surface 11 of the housing 10, and is in contactwith body fluid when the implantable device 1 is implanted.

The wireless communication module 20 is configured to wirelesslytransmit a signal based on the electrical signal output by the opticalsensor to the external wireless communication device 2. In other words,the wireless communication module 20 is configured to wirelesslytransmit a signal that is a function of the light detected by theoptical sensor 34, whether this be a function of the intensity of thelight, optical rotation of the light, or amount of refraction of thelight. As such, the signal is also a function of the concentration ofglucose in the body fluid in the vicinity of the implantable device 1.

The wireless signal transmitted by the wireless communication module 20to the external wireless communication device 2 can be processed by theexternal wireless communication device 2, or a different apparatus, toprovide an output which is dependent upon the glucose concentration ofthe body fluid being measured by the implantable device 1, such as avalue of glucose concentration. The implantable device 1 may becalibrated by first performing a standard blood glucose test using alancet.

In some embodiments, the implantable device 1 further comprises atemperature sensor 39, as shown in FIG. 2 . The temperature sensor 39 ispreferably located adjacent to or in the vicinity of the glucosemeasurement unit 30, but may be located anywhere within the implantabledevice 1 where it is desired to measure a temperature. The wirelesscommunication module 20 may be configured to wirelessly transmit asignal based on a temperature measured by the temperature sensor 39 tothe external wireless communication device 2. This signal may be a partof the aforementioned signal based on the electrical signal output bythe optical sensor 34, or may be a separate signal.

Some of the measurements and operations performed by the glucosemeasurement unit 30 as described herein are temperature dependent. Byproviding a temperature sensor 39 and taking a temperature measurement,the temperature can be taken into account when processing orinterpreting measurements made by the implantable device 1. Thetemperature sensor 39 is, however, optional, since a temperature couldbe measured using a device not forming part of the implantable device 1,or else could be approximated (for example it could be assumed that thetemperature inside a human body is 37° C.).

Some optical properties of fluids such as body fluids vary with theconcentration of glucose within the fluid. These optical propertiesinclude the specific rotation of the fluid (the angle of rotation oflinearly polarized light passing through the fluid over a certaindistance), the refractive index of the fluid, and the infraredabsorption spectrum of the fluid. According to some aspects of thepresent disclosure, one or more of these properties can be directly orindirectly determined by the implantable device 1. By providing anoutput based upon one or more of these properties, a value for theconcentration of glucose in a body fluid can be determined. The outputis provided using the light source 32 configured to emit light towardsthe light transmissive part 12 of housing 10 of the implantable device1, and the optical sensor 34 configured to detect light returned throughthe transmissive part 12 from the light source 32, wherein the output isan electrical signal based on the detected light, in particular theintensity of the detected light or the amount of refraction of thedetected light.

As discussed previously, when the implantable device 1 is implanted,body fluid will contact light transmissive part 12, on an outer surface11 of the housing 10. Light from the light source 32 passes throughlight transmissive part 12 and interacts with body fluid in contact withthe light transmissive part 12. The interaction may occur outside thehousing 10, within the body fluid itself, or at an interface between thebody fluid and light transmissive part 12.

At least part of the light that has interacted with the body fluidreturns through the light transmissive part 12 towards the inside of thehousing 10 and is detected by optical sensor 34. Interaction between thebody fluid and the light may involve optical rotation of the light bythe body fluid, absorption of at least part of the light by the bodyfluid, or reflection and/or refraction of the light at the interface.Thus the light emitted by the light source 32 is in some manner modifiedby the glucose in the body fluid. The amount of interaction/modificationis dependent upon the glucose concentration within the body fluid. Theoptical sensor 34 outputs an electrical signal based on the detectedlight, wherein the electrical signal will be a function of the amount ofmodification of the light by the body fluid, and hence a function of theglucose concentration in the body fluid.

The electrical signal may be processed within the implantable device 1,for example by control unit 26. The wireless communication module 20receives the electrical signal from the optical sensor 34 and wirelesslytransmits a signal based on the electrical signal to the externalwireless communication device 2. In other words, the wirelesslytransmitted signal is a function of the electrical signal, which is afunction of the glucose concentration in the body fluid.

The signal transmitted by the wireless communication module 20 to theexternal wireless communication device 2 may be further processed by aprocessor (not shown) of the external wireless communication device 2 toprovide a glucose concentration value for the body fluid.

According to some embodiments of the present disclosure, opticalrotation of linearly polarised light passing through the body fluid isdetected by the optical sensor 34.

Glucose is an optically active material. That is, the plane ofpolarization of linearly polarized light is rotated as it travelsthrough glucose. For a solution of glucose, the rotation angle α of theplane of polarization of the linearly polarized light is dependent uponthe concentration β of glucose in the solution, the path length L of thelight through the solution, the wavelength λ of the light, and thetemperature T of the glucose solution.

Specific rotation [α]^(T) _(λ) is an intrinsic property of a compound ina solution and is the angle of rotation of the plane of polarization ofa ray of monochromatic light that passes through a sample of a compoundin a solution, per unit distance-concentration product.

Specific rotation is dependent upon temperature of the solution andwavelength of the polarized light. The concentration of glucose in asolution can be determined by measuring the angle α through which theplane of polarization of linearly polarized light is rotated as ittravels through the solution, and the path length L of the linearlypolarized light through the solution. If the temperature T of thesolution and the wavelength λ of the linearly polarised light are knownor approximated, then a value for the specific rotation [α]^(T) _(λ) ofglucose can be looked-up for that temperature and wavelength. Theconcentration β of glucose in the solution can then be determined fromthe angle α, specific rotation [α]^(T) _(λ), and path length L accordingto the following equation:

$\lbrack\alpha\rbrack_{\lambda}^{\tau} = \frac{\alpha}{\beta \cdot L}$

It can be approximated that a significant amount of the optical rotationof linearly polarised light through a body fluid such as blood orinterstitial fluid is caused by glucose rather than other components ofthe body fluid. The optical activity of other components in the bodyfluid can therefore generally be disregarded. Therefore by determiningthe angle of rotation of linearly polarized light passing through bodyfluid, a good approximation of the glucose concentration within the bodyfluid can be determined. Determination of the glucose concentrationwithin the body fluid can be carried out by the implantable device 1,for example by the control unit 26, or by the external wirelesscommunication device 2.

Determining the glucose concentration may comprise processing theelectrical signal output by the optical sensor 34 or the signal based onthe electrical signal that is wirelessly transmitted to the externalwireless communication device 2, to determine a measurement value. Aglucose concentration value may be determined by comparing themeasurement value to a look-up table comprising a plurality ofmeasurement values and their corresponding glucose concentration values.

FIG. 3 shows a partial schematic cross-section of an implantable device1, such as the implantable device shown in FIG. 1B, wherein the glucosemeasurement unit 30 is configured to measure the rotation angle α oflinearly polarized light travelling through the body fluid.

The implantable device 1 of FIG. 3 is shown to comprise recess 14,however in some examples recess 14 may not be present. As shown in FIG.3 , the first side wall 15 and second side wall 16 of the recess 14 eachcomprise at least part of the light transmissive part 12. The lightsource 32 may be arranged within the housing 10 such that the lightemitted towards the light transmissive part 12 passes through the lighttransmissive first side wall 15 to a region outside the housing, beforereturning through the light transmissive second side wall 16 to bedetected by optical sensor 34, as indicated by the arrow in FIG. 3 . Insome examples the light source 32 and optical sensor 34 may be arrangedwithin the housing 10 such that the emitted light leaves and returnsthrough the same surface of the light transmissive part 12, for examplebottom surface 17, as illustrated in FIG. 4 and FIG. 5 .

As shown in FIG. 3 , light emitted from light source 32 is linearlypolarized by first linear polarizer 41 and emitted via lighttransmissive part 12 to a region outside the housing 10. This regionwill be within body fluid when the implantable device is implanted.

As with any of the embodiments disclosed herein, the implantable device1 may comprise at least one lens 46 arranged to focus light emitted fromthe light source 32. In particular, the lens 46 may focus the lightemitted from the first light source 32 towards a point outside thehousing 10, or to focus light towards the optical sensor 34.

FIG. 3 shows the lens 46 located within the housing 10, in an opticalpath between light source 32 and light transmissive part 12, howeverlens 46 may instead be located in any suitable location such as on asurface of the light transmissive part 12, on outer surface 11 of thehousing 10. FIG. 3 also shows first linear polarizer 41 located in anoptical path between light source 32 and lens 46, however first linearpolarizer 41 may in some examples be located along the optical pathafter the lens 46.

Linearly polarized light passing through the body fluid is opticallyrotated by the glucose within the body fluid so that the plane ofpolarization of the light is rotated by an amount dependent upon theconcentration of the glucose and the distance travelled by the lightthrough the glucose. The distance travelled by the light through theglucose can be determined prior to implantation of the device. Theoptical sensor 34 is configured to detect the optical rotation of thelinearly polarised light that has passed through the body fluid andreturned through the transmissive part 12 from the region outside thehousing 10. The optical sensor 34 is further configured to output anelectrical signal based on the detected optically rotated light. Theoutput is based on the rotation angle α of the linearly polarized light.

As shown in FIG. 3 , detecting the linearly polarised light returnedthrough the transmissive part from the region outside the housing thathas been optically rotated may comprise using a second linear polarizer42 located in an optical path between the light source 32 and opticalsensor 34, between the optical sensor 34 and the region outside thehousing 10. The plane of polarization of the second linear polarizer 42is rotated about the optical path with respect to the plane ofpolarization of the first linear polarizer 41, preferably such that itis substantially orthogonal to the plane of polarization of the firstlinear polarizer 41. As such, the amount of linearly polarized lightfrom the light source 32 and first linear polarizer 41 detected byoptical sensor 34 will be dependent upon the amount of optical rotationof the light. This optical rotation takes place as the linearlypolarized light passes through the body fluid containing glucose. Theamount of optical rotation, and therefore the amount of light detectedby optical sensor 34 will depend upon the concentration of glucose inthe body fluid. As such, the electrical signal output by the opticalsensor 34 is based on the amount of optical rotation of the linearlypolarized light and hence the concentration of glucose in the bodyfluid.

The implantable device 1 illustrated in FIG. 3 may be susceptible tointerference, for example from the optical sensor 34 detecting lightthat does not originate from the light source 32, such as ambient light.FIG. 4 shows a partial schematic cross-section of an implantable device1 similar to FIG. 3 , but configured for greater interferencesuppression. As for the implantable device 1 shown in FIG. 3 , theimplantable device 1 shown in FIG. 4 comprises recess 14, but thepresence of recess 14 is optional.

Similar to FIG. 3 , the implantable device 1 shown in FIG. 4 comprises alight source 32, first linear polarizer 41 and second linear polarizer42. However, here the glucose measurement unit 30 further comprises asecond optical sensor 36. The first optical sensor 35 and second opticalsensor 36 may each comprise one or more photodiodes.

As for the implantable device 1 of FIG. 3 , the first linear polarizer41 of FIG. 4 is arranged to linearly polarize light emitted from thelight source 32 through the light transmissive part 12 in a firstpolarization plane, this polarized light being emitted to a regionoutside the housing 10. The second linear polarizer 42 is arranged tolinearly polarize light from the region outside the housing 10 in asecond polarization plane substantially orthogonal to the first plane(i.e. rotated 90° about the optical axis). A third linear polarizer 43is arranged to linearly polarize light from the region outside thehousing 10 in a third polarization plane, wherein the third plane isparallel to the first plane (i.e. rotated 0° about the optical axis).

FIG. 4 shows three lenses 46 configured to focus light as mentionedpreviously. One or more of the lenses 46 may be arranged to the focuslight emitted from the light source 32 to a point or region outside thehousing 10, in the body fluid. The first optical sensor 35 and secondoptical sensor 36 may be arranged to detect light originating from thelight source 32 that has been reflected in the body fluid, for examplein the vicinity of the point or region outside the housing. The detectedlight may have been focused from the point or region outside the housing10 towards the first optical sensor 35 and second optical sensor 36 byone or more lenses 46. Exemplary optical paths are illustrated in FIG. 4by arrows.

The second linear polarizer 42 is arranged such that a first part of thelinearly polarized light emitted from the light source 32 to the regionoutside the housing 10 is incident on the second linear polarizer 35. Inother words, the second linear polarizer 42 is located in an opticalpath between the light source 32 and the first optical sensor 35,between the region outside the housing 10 and the first optical sensor35.

The third linear polarizer 43 is arranged such that a second part of thelinearly polarized light emitted from the light source 32 to the regionoutside the housing 10 is incident on the third linear polarizer 43. Inother words, the third linear polarizer 43 is located in an optical pathbetween the light source 32 and the second optical sensor 36, betweenthe region outside the housing 10 and the second optical sensor 36.

The first optical sensor 35 is arranged to detect the first part of thelinearly polarized light passing from the region outside the housing 10through the second linear polarizer 42. This first part of the linearlypolarized light originated from the light source 32, was linearlypolarized in a first plane by the first linear polarizer 41 before beingoptically rotated by the glucose in the body fluid, passing through thesecond linear polarizer 42, and being detected by the first opticalsensor 35.

The second optical sensor 36 is arranged to detect the second part ofthe linearly polarized light passing from the region outside the housing10 through the third linear polarizer 43. This second part of thelinearly polarized light originated from the light source 32, waslinearly polarized in a first plane by the first linear polarizer 41before being optically rotated by the glucose in the body fluid, passingthrough the third linear polarizer 43, and being detected by the secondoptical sensor 36.

The first optical sensor 35 and second optical sensor 36 are configuredto each output an electrical signal based on a detected light intensity,and therefore based on the angle through which the linear plane ofpolarization of light emitted by the light source 32 has been opticallyrotated. The complex signal S_(PD1) and complex signal S_(PD2) output bythe first optical sensor 35 and second optical sensor 36 respectivelycan be used to determine the angle α through which the linearlypolarized is rotated by the glucose using the following equation:

${\tan\alpha} = \frac{S_{{PD}2}}{S_{{PD}1}}$

By determining a value of a, a value corresponding to the glucoseconcentration of the body fluid can be determined, as discussedpreviously.

Signals S_(PD1) and S_(PD2) will be dependent upon factors such ascurrent passing through the light source 32, channel gain, type specificLED radiant intensity, ambient light, the transmission factor of theblood or other body fluid (a function of various factors such as type offood eaten and time since food eaten), and transmittance of the linearpolarizer. By providing the additional third linear polarizer 43 andsecond optical sensor 36, the electrical signals output by the firstoptical sensor 35 and second optical sensor 36 can be processed toreduce or remove the effects of the aforementioned factors upon whichthe signals S_(PD1) and S_(PD2) are otherwise dependent, for example toreduce the effects of interference, for example caused by ambient light,noise in electrical components of the implantable device 1, or similarparasitic effects. As such, a more accurate measurement of glucoseconcentration can be made, that is not dependent upon these factors.

FIG. 5 shows a further embodiment similar to FIG. 4 , however here theglucose measurement unit 30 further comprises a second light source 35,which again may comprise one or more LEDs. In a similar manner asdiscussed with reference to FIG. 4 , the light source 32 of FIG. 5(hereafter referred to as the first light source 32 with respect to FIG.5 ) is configured to emit light through the light transmissive part 12to a (first) region outside the housing 10 while the second light source35 is configured to emit light through the light transmissive part 12 toa (second) region outside the housing 10. The first region and secondregion may be identical.

The first linear polarizer 41 of FIG. 5 is arranged to linearly polarizelight emitted from the first light source 32 through the lighttransmissive part 12 in a first polarization plane, this light beingemitted to the first region outside the housing 10. The second linearpolarizer 42 is arranged to linearly polarize light from the firstregion outside the housing 10 in a second plane substantially orthogonalto the first plane (i.e. rotated 90° about the optical axis).

The fourth linear polarizer 44 of FIG. 5 is arranged to linearlypolarize light emitted from the second light source 35 through the lighttransmissive part 12 in a third polarization plane, this light beingemitted to the second region outside the housing 10.

The third linear polarizer 43 is arranged to linearly polarize lightfrom the second region outside the housing 10 in a fourth plane, whereinthe fourth plane is parallel to the third plane (i.e. rotated 0° aboutthe optical axis). The fourth plane may be parallel to the first plane.

The second linear polarizer 42 is arranged such that at least a part ofthe linearly polarized light emitted from the first light source 32 tothe first region outside the housing 10 is incident on the second linearpolarizer 42. In other words, the second linear polarizer 42 is locatedin an optical path between the first light source 32 and the firstoptical sensor 35, between the first region outside the housing 10 andthe first optical sensor 35.

The third linear polarizer 43 is arranged such that at least part of thelinearly polarized light emitted from the second light source 35 to theregion outside the housing 10 is incident on the third linear polarizer43. In other words, the fourth linear polarizer 44 is located in anoptical path between the second light source 35 and the second opticalsensor 36, between the second region outside the housing 10 and thesecond optical sensor 36.

The first optical sensor 35 is configured to be able to detect the atleast part of the linearly polarized light emitted from the first lightsource 32 (via the first region outside the housing 10), via the secondlinear polarizer 42. The second optical sensor 36 is configured to beable to detect the at least part of the linearly polarized light emittedfrom the second light source 35 (via the second region outside thehousing 10), via the third linear polarizer 433.

Preferably the first optical sensor 35 is arranged within theimplantable device 1 such that it does not detect light emitted by thesecond light source 35, while the second optical sensor 36 is arrangedwithin the implantable device 1 such that it does not detect lightemitted by the first light source 32. This reduces the effects ofinterference on the electrical signals output by the first opticalsensor 35 and second optical sensor 36.

The first optical sensor 35 and second optical sensor 36 are eachconfigured to output an electrical signal based on a detected lightintensity, and therefore based on the angle of optical rotation ofpolarized light from the first light source 32 or second light source35, as appropriate. The complex signal S_(PD1) and complex signalS_(PD2) output by the first optical sensor 35 and second optical sensor36 respectively can be used to determine the angle α through which thelinearly polarized is rotated by the glucose using the followingequation:

${\tan\alpha} = \frac{S_{{PD}2}}{S_{{PD}1}}$

The determined value of a can be used to determine a value correspondingto the glucose concentration of the body fluid, as discussed previously.

By providing the additional third linear polarizer 43, fourth linearpolarizer 44, and second optical sensor 36 in comparison to theimplantable device 1 of FIG. 3 , the electrical signals output by thefirst optical sensor 35 and second optical sensor 36 can be processed toreduce the effects of interference, for example caused by ambient light.As such, a more accurate measurement of glucose concentration can bemade.

In some embodiments, the glucose measurement unit is a refractometer,wherein the electrical signal output by the optical sensor 34 is basedon the refractive index n₂ of the body fluid in contact with the lighttransmissive part 12.

The refractive index n₂ of a body fluid containing glucose is a functionof (i.e. depends on the) glucose concentration within the body fluid. Asglucose concentration of a body fluid varies, so too does the refractiveindex of the body fluid. The refractive index of a body fluid can bedetermined using a refractometer. By determining the refractive index ofthe body fluid, a value of glucose concentration may be determined. Thismay involve use of a look-up table, as discussed with reference tooptical activity.

FIG. 6 shows a partial schematic cross-section of an implantable device1 in which the glucose measurement unit 30 is a refractometer. Therefractometer comprises a prism 60, wherein the light source 32 and theprism 60 are arranged such that the light emitted from the light source32 is incident on a surface 61 of the prism 60, via the prism 60. Inother words, and as shown by the arrows in FIG. 6 , the prism 60 andlight source 32 are positioned such that light emitted from light source32 enters prism 60 and travels through the prism 60 until it reachessurface 61 of the prism 60.

Body fluid will be in contact with surface 61 when the implantabledevice 1 is implanted. As such, the light transmissive part 12 comprisesthe prism 60.

Depending upon the angle of incidence θ₁ of the light upon the surface61, a portion of the light emitted from the light source 32 may bereflected at the surface 61 of the prism 60, at the body fluid-prisminterface (i.e totally internally reflected). The optical sensor 34 isarranged to detect this reflected portion of the light once it hasreturned through and exited the prism 60. In particular, the opticalsensor 34 is arranged to measure the angle of refraction θ₂ of the(totally internally) reflected light.

FIG. 6 shows the optical sensor 34 as a CCD sensor 62. The location ofthe reflected light on the CCD sensor 62 can be used to determine theangle of refraction θ₂ and therefore determine the refractive index ofthe body fluid in contact with the surface 61. The CCD sensor 62therefore outputs an electrical signal based on the refractive index ofthe body fluid.

The relationship between the angle of incidence θ₁, angle of refractionθ₂, refractive index n₁ of the prism 60 and refractive index n₂ of thebody fluid is given as:

$\frac{\sin\theta_{1}}{\sin\theta_{2}} = \frac{n_{2}}{n_{1}}$

Thus if the angle of incidence θ₁ and refractive index n₁ of the prism60 are already known, then by measuring the angle of refraction θ₂, avalue for the refractive index n₂ of the body fluid can be determined.The value for the refractive index of the body fluid can be used todetermine a value for the concentration of glucose in the body fluid,for example by comparing the value for the refractive index of the bodyfluid to a look-up table, or performing additional calculations on thevalue for the refractive index of the body fluid.

By using a refractometer to measure an angle of refraction, an accuratevalue of glucose concentration can be determined, since factors such asthe absolute brightness of light source 32 and the light transmission ofthe body fluid will not affect the angle of refraction and hence thedetermined value of glucose concentration.

In some embodiments, the glucose measurement unit is an infra-redspectrometer. The infrared absorption spectrum of a body fluidcontaining glucose will vary with glucose concentration. By measuringthe infra-red absorption of the body fluid, a value of glucoseconcentration may be determined. This may involve use of a look-uptable, as discussed with reference to optical activity.

FIG. 7 shows an embodiment in which the glucose measurement unit is aninfra-red spectrometer.

The light emitted by the light source 32 is infra-red light and isemitted through the light transmission part 12 to a region outside thehousing 10. The optical sensor 34 is configured to detect infra-redlight returned through the light transmissive part 12 from the lightsource 32, via the region outside the housing 10, and output anelectrical signal based on the detected light infra-red light, and thusbased on the glucose concentration in the body fluid.

Optionally, the glucose measurement unit 30 comprises a first filter 70configured to filter the light emitted by the light source 32 such thatonly light of a particular wavelength passes through the first filter 70and is emitted through the light transmissive part 12 to the regionoutside the housing 10. Optionally, the glucose measurement unit 30comprises a second filter 72 configured to filter the light returnedthrough the light transmissive part 12 from the light source 32, suchthat only light of a particular wavelength passes through the secondfilter 72 and is detected by the optical sensor 34. The optical sensor34 may be configured to detect a variable band of wavelengths of light.The band of wavelengths detected by the optical sensor 34 may beadjusted by changing a voltage applied to the optical sensor 34.

The present disclosure also relates to a system comprising an externalwireless communication device 2 and an implantable device 1 according toany of the aforementioned embodiments. FIG. 8 shows such a system whenthe implantable device 1 has been implanted into a blood vessel 3 of apatient 4 (such as a human or animal).

In a similar manner to the wireless communication module 20 of theimplantable device 1, the external wireless communication device 2comprises an antenna, power supply and control unit (not shown). Duringuse, the external wireless communication device 2 may be brought intoclose proximity of the implantable device 1. If the implantable device 1has been implanted into a patient 4, this may involve bringing theexternal wireless communication device 2 into the vicinity of the skin 5of the patient 4, for example within a distance d of less than around 2cm from the skin 5.

The external wireless communication device 2 wirelessly transmits powerto the implantable device 1 by electromagnetic induction between theantenna of the external wireless communication device 2 and the antenna22 of the implantable device 1. A current is induced in the antenna 22of the implantable device 1, providing power to any electrical circuitrywithin the device, such as the glucose measurement unit 30.

Responsive to receiving the power, or responsive to receiving anadditional wireless signal transmitted by the external communicationdevice 2 to the implantable device 1, the implantable device 1 proceedswith measuring the glucose concentration of body fluid in contact withthe housing 10 of the implantable device 1. The light source 32 of theimplantable device 1 emits light towards the light transmissive part 12of the housing 10 of the implantable device 1. The optical sensor 34 ofthe implantable device 1 detects light returned through the transmissivepart 12, and outputs an electrical signal based on the detected light.The wireless communication module 20 of the implantable device 1 isconfigured to wirelessly transmit a signal based on the electricalsignal to the external wireless communication device 2. The signalwirelessly transmitted to the external wireless communication device 2by the implantable device 1 may be processed (for example by theexternal wireless communication device 2) to determine a value ofglucose concentration for the body fluid.

The present disclosure also relates to a method of performing any of theaforementioned steps in relation to the implantable device 1 andexternal wireless communication device 2.

FIG. 9 shows a method according to embodiments of the presentdisclosure. At step 901, light is emitted by a light source 32 of anaforementioned implantable device 1 towards a light transmissive part 12of a housing 10 of the implantable device 1. At step 902, an opticalsensor 34 of the implantable device 1 detects light returned through thelight transmissive part 12 from the light source 32. At step 903, anelectrical signal based on the detected light is output by the opticalsensor 34. At step 904, a wireless communication module 20 of theimplantable device 1 wirelessly transmits a signal based on theelectrical signal to an external wireless communication device 1. Asdiscussed previously, the signal wirelessly transmitted to the externalwireless communication device 2 by the implantable device 1 may beprocessed (for example by the external wireless communication device 2)to determine a value of glucose concentration for the body fluid.

The terms “drug” or “medicament” are used synonymously herein anddescribe a pharmaceutical formulation containing one or more activepharmaceutical ingredients or pharmaceutically acceptable salts orsolvates thereof, and optionally a pharmaceutically acceptable carrier.An active pharmaceutical ingredient (“API”), in the broadest terms, is achemical structure that has a biological effect on humans or animals. Inpharmacology, a drug or medicament is used in the treatment, cure,prevention, or diagnosis of disease or used to otherwise enhancephysical or mental well-being. A drug or medicament may be used for alimited duration, or on a regular basis for chronic disorders.

As described below, a drug or medicament can include at least one API,or combinations thereof, in various types of formulations, for thetreatment of one or more diseases. Examples of API may include smallmolecules having a molecular weight of 500 Da or less; polypeptides,peptides and proteins (e.g., hormones, growth factors, antibodies,antibody fragments, and enzymes); carbohydrates and polysaccharides; andnucleic acids, double or single stranded DNA (including naked and cDNA),RNA, antisense nucleic acids such as antisense DNA and RNA, smallinterfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleicacids may be incorporated into molecular delivery systems such asvectors, plasmids, or liposomes. Mixtures of one or more drugs are alsocontemplated.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other solidor flexible vessel configured to provide a suitable chamber for storage(e.g., short- or long-term storage) of one or more drugs. For example,in some instances, the chamber may be designed to store a drug for atleast one day (e.g., 1 to at least 30 days). In some instances, thechamber may be designed to store a drug for about 1 month to about 2years. Storage may occur at room temperature (e.g., about 20° C.), orrefrigerated temperatures (e.g., from about −4° C. to about 4° C.). Insome instances, the drug container may be or may include a dual-chambercartridge configured to store two or more components of thepharmaceutical formulation to-be-administered (e.g., an API and adiluent, or two different drugs) separately, one in each chamber. Insuch instances, the two chambers of the dual-chamber cartridge may beconfigured to allow mixing between the two or more components prior toand/or during dispensing into the human or animal body. For example, thetwo chambers may be configured such that they are in fluid communicationwith each other (e.g., by way of a conduit between the two chambers) andallow mixing of the two components when desired by a user prior todispensing. Alternatively or in addition, the two chambers may beconfigured to allow mixing as the components are being dispensed intothe human or animal body.

The drugs or medicaments contained in the drug delivery devices asdescribed herein can be used for the treatment and/or prophylaxis ofmany different types of medical disorders. Examples of disordersinclude, e.g., diabetes mellitus or complications associated withdiabetes mellitus such as diabetic retinopathy, thromboembolismdisorders such as deep vein or pulmonary thromboembolism. Furtherexamples of disorders are acute coronary syndrome (ACS), angina,myocardial infarction, cancer, macular degeneration, inflammation, hayfever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs anddrugs are those as described in handbooks such as Rote Liste 2014, forexample, without limitation, main groups 12 (anti-diabetic drugs) or 86(oncology drugs), and Merck Index, 15th edition.

Examples of APIs for the treatment and/or prophylaxis of type 1 or type2 diabetes mellitus or complications associated with type 1 or type 2diabetes mellitus include an insulin, e.g., human insulin, or a humaninsulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1analogues or GLP-1 receptor agonists, or an analogue or derivativethereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or apharmaceutically acceptable salt or solvate thereof, or any mixturethereof. As used herein, the terms “analogue” and “derivative” refers toa polypeptide which has a molecular structure which formally can bederived from the structure of a naturally occurring peptide, for examplethat of human insulin, by deleting and/or exchanging at least one aminoacid residue occurring in the naturally occurring peptide and/or byadding at least one amino acid residue. The added and/or exchanged aminoacid residue can either be codable amino acid residues or othernaturally occurring residues or purely synthetic amino acid residues.Insulin analogues are also referred to as “insulin receptor ligands”. Inparticular, the term “derivative” refers to a polypeptide which has amolecular structure which formally can be derived from the structure ofa naturally occurring peptide, for example that of human insulin, inwhich one or more organic substituent (e.g. a fatty acid) is bound toone or more of the amino acids. Optionally, one or more amino acidsoccurring in the naturally occurring peptide may have been deletedand/or replaced by other amino acids, including non-codeable aminoacids, or amino acids, including non-codeable, have been added to thenaturally occurring peptide.

Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulinglulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28)human insulin (insulin aspart); human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Examples of insulin derivatives are, for example,B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®);B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin;B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 humaninsulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30)human insulin (insulin degludec, Tresiba®);B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, forexample, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®,Bydureon®, a 39 amino acid peptide which is produced by the salivaryglands of the Gila monster), Liraglutide (Victoza®), Semaglutide,Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®),rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C, CM-3,GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen,Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701,MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030, CAM-2036, DA-15864,ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.

An examples of an oligonucleotide is, for example: mipomersen sodium(Kynamro®), a cholesterol-reducing antisense therapeutic for thetreatment of familial hypercholesterolemia.

Examples of DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Examples of hormones include hypophysis hormones or hypothalamushormones or regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Examples of polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)2 fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region. The term antibody also includes anantigen-binding molecule based on tetravalent bispecific tandemimmunoglobulins (TBTI) and/or a dual variable region antibody-likebinding protein having cross-over binding region orientation (CODV).

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentdisclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific,tetraspecific and multispecific antibodies (e.g., diabodies, triabodies,tetrabodies), monovalent or multivalent antibody fragments such asbivalent, trivalent, tetravalent and multivalent antibodies, minibodies,chelating recombinant antibodies, tribodies or bibodies, intrabodies,nanobodies, small modular immunopharmaceuticals (SMIP), binding-domainimmunoglobulin fusion proteins, camelized antibodies, and VHH containingantibodies. Additional examples of antigen-binding antibody fragmentsare known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen. Examples ofantibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g.,Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

Pharmaceutically acceptable salts of any API described herein are alsocontemplated for use in a drug or medicament in a drug delivery device.Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Those of skill in the art will understand thatmodifications (additions and/or removals) of various components of theAPIs, formulations, apparatuses, methods, systems and embodimentsdescribed herein may be made without departing from the full scope andspirit of the present disclosure, which encompass such modifications andany and all equivalents thereof.

Although claims have been formulated in this application to particularcombinations of features, it should be understood that the scope of thedisclosure also includes any novel features or any novel combinations offeatures disclosed herein either explicitly or implicitly or anygeneralization thereof, whether or not it relates to the same disclosureas presently claimed in any claim and whether or not it mitigates any orall of the same technical problems as does the present disclosure. Theapplicant hereby gives notice that new claims may be formulated to suchfeatures and/or combinations of features during the prosecution of thepresent application or of any further application derived therefrom.

Although several embodiments have been shown and described, it would beappreciated by those skilled in the art that changes may be made inthese embodiments without departing from the principles of thedisclosure, the scope of which is defined in the claims.

1. An implantable device for measuring a glucose concentration of a bodyfluid, the implantable device comprising: a first light sourceconfigured to provide a first polarized light, a first linear polarizerconfigured to provide a second polarized light by linearly polarizing afirst part of the first polarized light, a first optical sensorconfigured to detect the second polarized light and output a firstelectrical signal based on the detected second polarized light, a secondlinear polarizer configured to provide a third polarized light bylinearly polarizing a second part of the first polarized light or afourth polarized light provided by a second light source, and a secondoptical sensor configured to detect the third polarized light, andoutput a second electrical signal based on the detected third polarizedlight; and a communication module configured to transmit a signal to anexternal communication device, the signal being based on the firstelectrical signal and the second electrical signal.
 2. The implantabledevice according to claim 1, wherein the implantable device isconfigured to wirelessly receive power from the external communicationdevice.
 3. The implantable device according to claim 1, wherein theimplantable device is dimensioned to be implantable into a human bloodvessel.
 4. The implantable device according to claim 1 configured suchthat the first polarized light is emitted through a light transmissivepart of a housing of the implantable device and the first part of thefirst polarized light is received through the light transmissive part.5. The implantable device according to claim 1, further comprising atleast one lens arranged to focus the first polarized light emitted fromthe first light source.
 6. The implantable device according to claim 1,wherein the first light source is arranged to provide the firstpolarized light linearly polarized in a first plane, wherein the firstlinear polarizer is arranged to linearly polarize the first part of thefirst polarized light in a second plane substantially orthogonal to thefirst plane, and wherein the second linear polarizer is arranged tolinearly polarize the second part of the first polarized light or thefourth polarized light in a third plane, wherein the third plane issubstantially parallel to the first plane.
 7. The implantable deviceaccording to claim 1, wherein the implantable device comprises thesecond light source.
 8. The implantable device according to claim 1,wherein the communication module is a wireless communication moduleconfigured to wirelessly transmit the signal to the externalcommunication device.
 9. The implantable device according to claim 1,wherein the implantable device is capsule-shaped.
 10. The implantabledevice according to claim 1, further comprising a temperature sensor,wherein the communication module is configured to transmit a temperaturesignal based on a temperature measured by the temperature sensor to theexternal communication device.
 11. The implementable device of claim 1,wherein the first linear polarizer is arranged to linearly polarize thefirst part of the first polarized light in a first plane, and the secondlinear polarizer is arranged to linearly polarize the second part of thefirst polarized light or the fourth polarized light in a second plane,and wherein first plane is non-parallel with the second plane.
 12. Asystem comprising: an implantable device for measuring a glucoseconcentration of a body fluid, the implantable device comprising: afirst light source configured to provide a first polarized light, afirst linear polarizer configured to provide a second polarized light bylinearly polarizing a first part of the first polarized light, a firstoptical sensor configured to detect the second polarized light andoutput a first electrical signal based on the detected second polarizedlight, a second linear polarizer configured to provide a third polarizedlight by linearly polarizing a second part of the first polarized lightor a fourth polarized light provided by a second light source, a secondoptical sensor configured to detect the third polarized light and outputa second electrical signal based on the detected third polarized light,and a communication module; and an external communication device,wherein the communication module of the implantable device is configuredto transmit a signal to the external communication device, the signalbeing based on the first electrical signal and the second electricalsignal.
 13. The system according to claim 12, wherein the externalcommunication device comprises a smartphone.
 14. A method comprising:providing an implantable device for measuring a glucose concentration ofa body fluid, the implantable device comprising: a first light sourceconfigured to provide a first polarized light, a first linear polarizerconfigured to provide a second polarized light by linearly polarizing afirst part of the first polarized light, a second linear polarizerconfigured to provide a third polarized light by linearly polarizing asecond part of the first polarized light or a fourth polarized lightprovided by a second light source, a first optical sensor configured todetect the second polarized light and to output a first electricalsignal based on the second polarized light that has been detected by thefirst optical sensor, a second optical sensor configured to detect thethird polarized light and to output a second electrical signal based onthe third polarized light that has been detected by the second opticalsensor, and a communication module configured to communicate with anexternal communication device; emitting the first polarized light by thefirst light source of the implantable device; detecting, by the firstoptical sensor of the implantable device, the second polarized light;detecting, by the second optical sensor of the implantable device, thethird polarized light; outputting, by the first optical sensor, a firstelectrical signal based on the second polarized light that has beendetected by the first optical sensor; outputting, by the second opticalsensor, a second electrical signal based on the third polarized lightthat has been detected by the second optical sensor; and transmitting,by the communication module of the implantable device, a signal based onthe first electrical signal and the second electrical signal to anexternal communication device.
 15. The system according to claim 14,wherein the implantable device is configured to wirelessly receive powerfrom the external communication device.
 16. The system according toclaim 14, wherein the communication module is a wireless communicationmodule configured to wirelessly transmit the signal to the externalcommunication device.
 17. The system according to claim 14, wherein theimplantable device is configured such that the first polarized light isemitted through a light transmissive part of a housing of theimplantable device and the first part of the first polarized light isreceived through the light transmissive part.
 18. The system accordingto claim 14, wherein the implantable device further comprises at leastone lens arranged to focus the first polarized light.
 19. The systemaccording to claim 14, wherein the implantable device is capsule-shaped.20. The system of claim 14, wherein the first linear polarizer isarranged to linearly polarize the first part of the first polarizedlight in a first plane, and the second linear polarizer is arranged tolinearly polarize the second part of the first polarized light or thefourth polarized light in a second plane, and wherein first plane isnon-parallel with the second plane.